2.1 Transnorsertraline
Transnorsertraline, i.e., (1R,4S)-trans-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine and (1S,4R)-trans-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine are described in, for example, U.S. Pat. No. 7,087,785 B2 (“the '785 patent”; incorporated herein by reference in its entirety), have the following chemical structures, respectively:

Uses of transnorsertraline in the treatment, prevention, or management of affective disorders and other various CNS disorders are also disclosed in the '785 patent. Such disorders include, but are not limited to, depression, mood disorders, anxiety disorders, behavioral disorders, eating disorders, substance abuse disorders, and sexual function disorders.
2.2 Salts and Polymorphic Forms
Whether crystalline or amorphous, potential solid forms of a pharmaceutical compound include single-component and multiple-component solids. Single-component solids consist essentially of the pharmaceutical compound in the absence of other compounds. Variety among single-component crystalline materials may potentially arise, e.g., from the phenomenon of polymorphism, wherein multiple three-dimensional arrangements exist for a particular pharmaceutical compound (see, e.g., S. R. Byrn et al., Solid State Chemistry of Drugs, (1999) SSCI, West Lafayette).
Solid forms such as salts, crystal forms, e.g., polymorphic forms of a compound are known in the pharmaceutical art to affect, for example, the solubility, stability, flowability, fractability, and compressibility of the compound as well as the safety and efficacy of drug products based on the compound, (see, e.g., Knapman, K. Modern Drug Discoveries, 2000:53).
The importance of studying polymorphs was underscored by the case of ritonavir, an HIV protease inhibitor that was formulated as soft gelatin capsules. About two years after the product was launched, the unanticipated precipitation of a new, less soluble polymorph in the formulation necessitated the withdrawal of the product from the market until a more consistent formulation could be developed (see S. R. Chemburkar et al., Org. Process Res. Dev., (2000) 4:413-417). Thus, the preparation of solid forms is of great importance in the development of a safe, effective, stable and marketable pharmaceutical compound.
New salts and polymorphic forms of transnorsertraline can further the development of formulations for the treatment, prevention or management of CNS diseases.
2.3 Treatment of Neurological Disorders
Serotonin, i.e., 5-HT, is known to play an important role in the treatment of various CNS disorders. Among others, 5-HT1A (serotonin 1A) receptors provide an important mechanism for controlling 5-HT release in the brain. These receptors are located presynaptically in the raphe nuclei where they function as autoreceptors to inhibit the firing rate of 5-HT neurons. 5-HT1A receptors are also located postsynaptically in corticolimbic regions where they also reduce firing activity of 5-HT neurons. At the initiation of treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), the 5-HT1A autoreceptors are activated by 5-HT, leading to a reduction in 5-HT neuronal firing. As SSRI or SNRI treatment continues, however, 5-HT1A autoreceptors become desensitized, and the firing activity is restored. This adaptive change is believed to contribute, at least in part, to the delay in efficacy of SSRIs and SNRIs in treating various neurological disorders.
Therefore, a need exists for the treatment, prevention, or management of various neurological disorders, wherein the desensitization of 5-HT receptors may be minimized and the increase in 5-HT neuronal firing may be maintained.